At present, the understanding of pathophysiology of solid tumors is increasingly turning to their unique growth microenvironments. The center areas of the solid tumors are characterized by increased interstitial pressure, lowered cell pH, low oxygen content and tumor cell heterogeneity. The tumor microenvironments are also an important reason for tumor metastasis, invasion and insensitivity to conventional radiotherapy and chemotherapy. First, the solid tumors contain hypoxic or necrotic areas, the hypoxic areas are far away from the blood vessels and are not rich in blood supply, and high interstitial pressure exists in the tumor centers, so that the tumor cells in the hypoxic areas difficulty obtain effective medicine concentration, and thus the hypoxic areas cannot be effectively treated by the conventional chemotherapy. Second, radiotherapy relies on the formation of oxygen free radicals, resulting in DNA damage in mitotic cells, so the lack of the oxygen free radicals in the tumor centers reduces the DNA damage during processing. Third, most chemotherapeutic medicines are effective only for rapid dividing tumor cells, and have poor efficacy in hypoxic tumor cells, stromal cells, and tumor tissue structures that have ceased to divide (fibronectin and collagen). Moreover, the conventional radiotherapy and chemotherapy often lack specific effects on tumor cells. The tumor anaerobic microenvironments limit the efficacy of the conventional radiotherapy and chemotherapy as well as viral therapy, but provide a good opportunity for anaerobic bacteria to grow and play oncolysis effects in the hypoxic areas of the tumors.
DCG is obligate anaerobe Gram-positive bacillus, which has two growth states: spore and vegetative states. DCG spores are very weak in antigen property, and can be used as a preparation for intravenous injection to reduce the organism stimulation. Due to disordered vascular tissue structures of the tumors, the DCG spores in the blood can easily enter the tumor tissues, and germinate, reproduce, and secret lipase, protease and other hydrolases in the tumor hypoxic/necrotic areas to effectively and indiscriminately destroy various cells (tumor cells, non-cancerous interstitial cells, active dividing cells, stem cells or resting cells, etc.) and tumor structures (fibronectin and collagen) in the tumor tissue, causing oncolytic necrosis of the most of the tumors and achieving all the parenchyma and interstitial digestion of the tumors. The tumor microenvironments are destroyed and altered fundamentally. The destroying of the tumor microenvironments effectively restrains or reverses the tumor growth and destroys the tumor-forming condition, and even leads to the almost complete destroying and disappearance of the whole tumors, thereby being possible for NSCLC deep processing. The hydrolases secreted by DCG dissolve tumor tissue-induced inflammatory response and directly involve in the destroying of reactive oxygen species, protease and other degrading enzymes on the tumor cells. More importantly, the inflammatory response can stimulate the organism to produce a strong cellular immune response, and destroy the residual tumor cell microenvironments.
Chinese Patent CN103374538A (Application No. 201210310374.4) discloses a derivative bacterial strain of avirulent and non-pathogenic Clostridium ghonii, which is capable of inhibiting the growth of one or more solid tumors, and reversing or destroying one or more solid tumors. CN103374538A also relates to a composition of derivative bacterial strain, targeting the dissolution of the solid tumors.
However, due to the different formation reasons of the solid tumors, the effects of different strains on the solid tumors are specific. Therefore, further study on the specific effects of different strains on different solid tumors has become a hotspot in this field.